Dr. Philip Greenberg

Philip D. Greenberg, M.D.
Professor of Medicine (Oncology) and Immunology

Dr. Greenberg graduated from Washington University with a degree in biology. He received his M.D. summa cum laude from the State University of New York, Downstate Medical Center, in 1971. After completing postdoctoral training at the University of California at San Diego, he joined the Fred Hutchinson Cancer Research Center and the Division of Oncology at the University of Washington in 1976. He is currently the Head of the Program in Immunology at the Fred Hutchinson Cancer Research Center.

Dr. Greenberg's laboratory is involved in studies elucidating the immunobiology of host T cell responses to infectious viruses and transformed cells. Analysis of T cell responses to pathogenic viral infections and tumors has demonstrated that reactive T cells are often rendered anergic or dysfunctional as a consequence of encounter with the antigen, and the basis for these defects are being explored and molecular strategies to restore and augment T cell function via genetic modification of T cells with vectors expressing novel proteins, dominant negative proteins, or RNAi are being evaluated. The mechanisms of tolerance to tumor antigens that are over-expressed pro-oncogenic self-proteins are being examined in transgenic mouse models that express tumor-derived proteins of known immunogenicity under the control of tissue-specific promoters- these models are making it possible to isolate and track antigen-specific tolerant cells, to use technologies such as gene expression arrays to identify abnormalities in tolerant T cells, and to begin testing molecular strategies for correcting defects. Immunity to human pathogenic viruses is being studied with the goal of defining methods to generate or augment protective immune responses. These studies include the development of transgenic/knock-in mice in which human genes are being expressed to create models that better typify human immune responses, and these mice are being used to evaluate and improve the design of candidate HIV vaccines. Previous studies of human CMV immunobiology led to a clinical trial in which immunosuppressed leukemia patients at high risk for fatal CMV infection were infused with CMV-specific cytolytic T cell clones. The clones had been previously selected for recognition of an immunodominant protective epitope and expanded to large numbers in vitro, and this trial demonstrated that T cell transfer can reconstitute immunity in humans and provide protection from disease. This adoptive therapy approach with cloned T cells of known function and specificity is now being pursued to both elucidate the immunobiology of human malignancies and infections and to develop novel immune-based therapies. Clinical trials of adoptive T cell therapy are now underway in patients with leukemia. Methods to modulate the effector functions, survival, target avidity, and localization of T cells, and to impart desired antigen specificity are being developed using retroviral-mediated gene transfer, and such engineered T cell clones are now being evaluated in mouse models and will soon be tested in treatment of human disease.

Students currently training in the Greenberg Lab: Cassie Chou, Amanda McIntyre

Honors and Awards

• American Society of Clinical Investigation (Elected 1987)
• Alpha Omega Alpha (Elected 1970)
• Graduation from Medical School Summa Cum Laude (1971)
• USPHS Individual Postdoctoral Research Fellowship (1974-1976)
• American Cancer Society Junior Clinical Faculty Fellowship (1978-1981)
• National Institutes of Health MERIT Award (1991-1999)
• Association of American Physicians (Elected 1998)
• National Institutes of Health MERIT Award (1999-2007)
• Fellow, American Association for the Advancement of Science (elected 2007)
• Fellow, American College of Physicians (elected 2008)

Professional Societies

• American Association of Immunologists (Member, 1982 to date)
• American Society of Gene Therapy (Charter Member)

Certification

• June, 1974 - American Board of Internal Medicine

National Responsibilities

• Member, Clinical Cancer Program Project Review Committee of the National Cancer Institute, National Institutes of Health (1982,1983)
• Member, Special Study Section for the Biological Response Modifiers Program of the National Cancer Institute, National Institutes of Health (1983)
• Consulting Member, Biological Response Modifiers Program Decision Network Committee, Division of Cancer Treatment, National Cancer Institute (1982 - 1985)
• Chairman, Special Study Section for the National Institutes of Health (August 1983)
• Member, Immunobiology Study Section, National Institutes of Health (Term: 1984 - 1989)
• Member, U.S.-Japan Cancer Research Cooperation Program, Committee on Tumor Immunology (1985 to 1989)
• Member, NIH Reviewer Reserve Board (1989-1993)
• American Association of Cancer Research, Washington Legislative Committee (1990-1994)
• Board of Scientific Counselors, NCI, Division of Cancer Treatment (1992-1996)
• Chairman, Review of NCI Intramural Program--Laboratory of Molecular Immunoregulation (1992)
• Member, American Association of Immunologists Public Affairs Committee (1992-1995)
• Member, Scientific Advisory Council of the Cancer Research Institute (1995 - Present)
• Member, Biologic Subcommittee of the NIH Developmental Therapeutics Program Review Group (1997 - 2003)
• Member, American Society of Gene Therapy Education Committee (1997 - 1999)
• Chairman, American Society of Gene Therapy, Nominating Committee (1997 - 1998)
• Member, NIH Office of AIDS Research Advisory Council (1998 - 2002)
• Member, Scientific Advisory Board, Abrahamson Cancer Research Institute at the University of Pennsylvania (1999 – Present)
• Damon Runyon-Walter Winchell Foundation, Clinical Investigator Award Committee (1999-Present)
• Member, Scientific Advisory Board, Johns Hopkins University Cancer Center (2001-Present)
• Chair, Scientific Advisory Board, NCCR program, Ludwig Institute for Cancer Research, Lausanne, Switzerland (2002 - present)

Editorial Boards and Responsibilities

• Associate Editor, Journal of Immunology, Tumor Immunology Section (1982-1985)
• Editorial Head for the Tumor Immunology Section, Journal of Immunology (1985-1989)
• Member, Program Committee for American Association of Immunologists (FASEB); Chairman, Tumor Immunology Block  (1986-1989)
• Advisory Editor, Progress in Experimental Tumor Research, Volume 32: "Immunomodulation of Neoplasia".
• Editorial Advisory Board, Journal of National Cancer Institute (1988 to 1990)
• Editorial Board, Therapeutic Immunology (1993-1998)
• Editorial Board, Human Gene Therapy (1993 - Present)
• Editorial Board, Gene Therapy (1993 - 2002)
• Editorial Board, Clinical Cancer Therapy (1994 - 1997)
• Editorial Board, Molecular Therapy (1999 – Present)
• Program Committee for American Association of Immunologists (FASEB); Chair, Tumor Immunology Block (1996 - 2000)
• Editorial Board, Cancer Cell (2002 - Present)
• Editorial Board, Cancer Immunology and Immunotherapy (2001 – Present)